Ion trap mass analyzers have been described extensively in the literature (see, e.g., March et al., “Quadrupole Ion Trap Mass Spectrometry”, John Wiley & Sons (2005)) and are widely used for mass spectrometric analysis of a variety of substances, including small molecules such as pharmaceutical agents and their metabolites, as well as large biomolecules such as peptides and proteins. Mass analysis is commonly performed in ion traps by the resonant excitation method, wherein a resonant ejection voltage is applied across a pair of electrodes while the amplitude of the main radio-frequency (RF) trapping voltage is ramped, causing ions to come into resonance and be ejected from the ion trap to the detector(s) in order of their mass-to-charge ratios (m/z's).
It is known that the characteristics of a mass spectral peak, e.g., peak height, width, and isotope spacing/ratio, acquired by resonant ejection will vary with the amplitude of the resonant ejection voltage, and that the amplitude that optimizes certain peak characteristics depends on the m/z of the ejected ion. The prior art contains a number of references that describe methods for varying the resonant ejection voltage amplitude during an analytical scan in order to produce high quality mass spectral peaks across the measured range of m/z's. For example, U.S. Pat. No. 5,298,746 to Franzen et al. (“Method and Device for Control of the Excitation Voltage for Ion Ejection from Ion trap Mass Spectrometers”) prescribes controlling the resonant ejection voltage during the analytical scan such that its amplitude is set proportionally to the square root of the main RF trapping voltage amplitude. In another example, U.S. Pat. No. 5,572,025 to Cotter et al. (“Method and Apparatus for Scanning an Ion Trap Mass Spectrometer in the Resonance Ejection Mode”) discloses operating an ion trap to maintain a constant ratio between the RF trapping voltage and resonant ejection voltage amplitudes. Many commercially available ion trap mass spectrometers utilize a calibration procedure in which the resonant ejection voltage amplitude that optimizes one or more peak characteristics (e.g., peak width) is experimentally determined for each of several calibrant ions having different m/z's, and an amplitude calibration is developed by fitting a line or curve to the several (m/z, amplitude) points.
It has been observed, however, that a simple relation between m/z and resonant ejection voltage amplitude may not provide optimized performance when an ion trap is operated under certain conditions, such as when the resonant ejection voltage and main RF trapping voltage are maintained in a phase-locked state, and/or when low ion trap pressures are utilized. Experimental studies of ion traps operated under such conditions indicate that as the resonant ejection voltage amplitude is varied, several regions of acceptable peak characteristics are seen, separated by transition regions having poor peak characteristics. Against this background, there is a need for a method for calibrating and operating an ion trap mass spectrometer operated under conditions which produce behavior more complex than is addressed by prior art methods.